Biosynthesis of Fatty Acids and Eicosanoids:- Desaturation of Fatty Acids Requires a Mixed-Function Oxidase
Palmitate and stearate serve as precursors of the two most common monounsaturated fatty acids of animal tissues: palmitoleate, 16:1(Δ9), and oleate, 18:1(Δ9); both of these fatty acids have a single cis double bond between C-9 and C-10 (see Table 10–1). The double bond is introduced into the fatty acid chain by an ox idative reaction catalyzed by fatty acyl–CoA desaturase (Fig. 21–13), a mixed-function oxidase (Box 21–1). Two different substrates, the fatty acid and NADH or NADPH, simultaneously undergo two-electron oxidations. The path of electron flow includes a cytochrome (cytochrome b5) and a flavoprotein (cytochrome b5 reductase), both of which, like fatty acyl–CoA desaturase, are in the smooth ER. Bacteria have two cytochrome b5 reductases, one NADH-dependent and the other NADPH-dependent; which of these is the main electron donor in vivo is unclear. In plants, oleate is produced by a stearoyl-ACP desaturase in the chloroplast stroma that uses reduced ferredoxin as the electron donor.
Mammalian hepatocytes can readily introduce double bonds at the Δ9 position of fatty acids but cannot introduce additional double bonds between C-10 and the methyl-terminal end. Thus, mammals cannot synthesize linoleate, 18:2(Δ 9,12), or α-linolenate,18:3(Δ 9,12,15) Plants, however, can synthesize both; the desaturases that introduce double bonds at the Δ12 and Δ15 positions are located in the ER and the chloroplast. The ER en zymes act not on free fatty acids but on a phospholipid, phosphatidylcholine, that contains at least one oleate linked to the glycerol (Fig. 21–14). Both plants and bacteria must synthesize polyunsaturated fatty acids to ensure membrane fluidity at reduced temperatures.
Because they are necessary precursors for the syn thesis of other products, linoleate and linolenate are essential fatty acids for mammals; they must be obtained from dietary plant material. Once ingested, linoleate may be converted to certain other polyunsaturated acids, particularly γ-linolenate, eicosatrienoate, and arachidonate (eicosatetraenoate), all of which can be made only from linoleate (Fig. 21–12). Arachidonate, 20:4(Δ5,8,11,14), is an essential precursor of regulatory lipids, the eicosanoids. The 20-carbon fatty acids are synthesized from linoleate (and linolenate) by fatty acid elongation reactions analogous to those described on page 797.
FIGURE 21–14 Action of plant desaturases. Desaturases in plants oxidize phosphatidylcholine-bound oleate to polyunsaturated fatty acids. Some of the products are released from the phosphatidylcholine by hydrolysis.
